Estudo farmacológico de extratos secos padronizadosde folhas de Picrolemma sprucei hookcoletadas na Amazônia Ocidental.

Abstract

Picrolemma sprucei (Simaroubaceae) known as caferana, is widely distributed in the Amazonian Region. The tea of the leaves and the roots is used to treatgastritis, fever, as anti-helminthic and as anti-malarial. Considering the ethnobotanical information and the small numbers of works with proven activities, this work proposes a pharmacological study with a standardized extract obtained from the plant leaves on behavior and vital functions in rodents, and also to analyze the molecular mechanisms responsible for the observed effects. The plant leaves were collected in Manaus/AM, dried in the shade and ground. The aqueous extract (AE) was obtained from the leaves infusion (2.5%), yielding 15%, and the butanolic fraction (BuF) was obtained from the AE partition with butanol. The BuF purification in HPLC yielded 4 fractions with RTs: F1=5,4 to12 min, F2 =12,1 to 19 min, F3=19,1 to 27,7 min; F4= 27,8 to 38 min. The oral administration of AE or BuF (1,0 g/kg) was lethal within 24 h. The treatment with AE (0,1 to 1,0 g/kg, p.o.) caused hypothermia and reduced the cold stress-induced gastric ulcers in mice. The AE, BuF and F4 inhibited the gastric acid secretion in rats with pylorus ligation. However, the AE (1 to 300 µg/mL) did not inhibit the H+-K+-ATPase pump in vitro. In anesthetized rats, the BuF (3 mg/kg, e.v.) produced a double depression on the arterial blood pressure (BP) and on the heart rate (HR): the doseof 3.0 mg/kg reduced the BP by 22 mm Hg and the HR by 20 bpm with the maximal effect after 1,5 min and reversion in 5 minutes; this effect was followed by late long lasting hypotension (90 mm Hg), concomitant to a HR decrease. Vagotomy or atropine (0.1 mg/kg e.v.) blocked the later effects on BP and on HR. The fractions F1 (0.2 to 5.4 mg/kg, e.v.) and F3 (0.3 to 2.4 mg/kg, e.v.) caused hypotension (5 to 40 mm Hg) related to the doses. The BuF (10 to 100 µg/mL) inhibited the spontaneous beats of the isolated rat right atrium without altering the BuF inotropic effect in the isolated left atrium. In aorta rings with intact endothelium, the tonus induced by noradrenalin was relaxed with BuF incubation. This effect was not abolished by the endothelium mechanicaldestruction, indicating a NO sintase independent mechanism of action. The AE and the BuF oral administration were lethal at the highest dose; the F4 fraction was identified as the lethal fraction of BuF. The toxic effect of AE and BuF was delayed on time and probably unrelated to the original plant extract, but to compounds produced during their liver metabolism.